Application of Genetic Testing for CYP 450 Polymorphism to Predict Response to Clopidogrel Inpatient Undergoing PCI

Abstract

Introduction: The anti-platelet agent clopidogrel is a commonly prescribed medication in patients in patients who are undergoing percutaneous coronary intervention. Response to clopidogrel varies substantially due to genetic and acquired factors. Patients who experience recurrent cardiovascular ischemic or thrombotic events while taking clopidogrel are typically described as non-responsive or resistant. In our study was planned to assess the utility of pharmaco-genetic testing (CYP2C19) for clopidogrel response and application of the data for modification of anti-platelet regimen accordingly. Methods: This is a prospective nonrandomized ethical committee approved study from our institute. We included the post PCI patients presented with chronic stable angina and acute coronary syndrome (who has less bleeding risk score) with good left ventricular function. Along with the demographic and clinical features, we collected the data of platelet aggregation test (light transmission of aggregometry), CYP2C19 genetic analysis test and clinical outcome at the time of discharge, at 15days of discharge and end of 3 months. CYP2C19 genetic analysis is done by method of DNA based clopidogrel resistance genotyping test. We grouped the cases as extensive metabolizers (EM) and intermediate metabolizers (IM) depending on CYP2C19genetic analysis into two groups.Results: A total of 33 patients are included in this study. Among 33 cases, 25(75.7%) cases are male patients and 8(24.2%) cases are female patient, 18 (54.5%) patients are diabetic Mellitus, 20(60.6%) patient are hypertensives, 7(21.2%) cases are smokers and 5 (15.1%) case are alcoholic. We have diagnosed 20(60.6%) cases of unstable angina and 13(39.4%) cases of chronic stable angina. The average Meheran bleeding risk score is 9.8. Age, risk factors are comparable between the the EM and IM group. But presentation of ACS is more in IM (p=0.001).Follow up at 3 months, one died suddenly (probable stent thrombosis) in EM group. No other MACE occurred in both the groups. Multivariate analysis with binary logistic regression showed that only presentation as ACS is statistically significant in IM (p=0.001). Platelet aggregation showed tendency towards statistical significance (p=0.08) in EM patient. With all other parameters including MACE (p=0.3), there is no statistical significance by multivariate analysis.Conclusion: In our small prospective clinical and genetic analysis of clopidogrel metabolizer status has shown that intermediate metabolizer status of the patient is statistically more in unstable angina (p=0.003). There is tendency for statistically significance between the platelet aggregation test (p=0.08) and extensive metabolizer status of the patient. Whatever may be the status of the clopidogrel metabolizing condition, there is no difference in MACE.